Researchers are investigating the safety and effectiveness of a new gene therapy product that replaces the defective β-sarcoglycan gene.

Limb-girdle muscular dystrophy type 2E (LGMD2E) is just one of approximately 20 subtypes of LGMD. The genetic mutations and molecular processes responsible for each subtype is distinct and requires a specialized gene therapy approach – despite the fact that the epidemiology and symptoms are similar across subtypes.

LGMD2E is characterized by widespread, progressive muscle wasting, initial pelvic and shoulder girdle weakness, degrees of proximal weakness and evidence of Gower’s maneuvers. Individuals with LGMD2E will often present with difficulty running, jumping or climbing stairs. Additionally, more than 50 percent of patients also experience cardiac dysfunction. LGMD2E affects males and females equally, with symptoms appearing in early childhood. No treatment is currently established.

LGMD2E is caused by a mutant β-sarcoglycan gene that limits expression of the full-length normal protein. This leads to a fragile muscle membrane, easily damaged with normal daily activity. At Nationwide Children’s Hospital, a phase I/IIa clinical trial is underway to use intravenous AAV9-mediated gene therapy to replace the defective β-sarcoglycan gene found in individuals with LGMD2E. The trial is led by Jerry Mendell, MD, attending neurologist and principal investigator in the Center for Gene Therapy in The Research Institute at Nationwide Children’s.

“We’re excited about what we can learn from this trial and how it will inform the future of gene therapy for LGMD patients,” says Dr. Mendell. “This early-phase trial is designed to test the safety and effectiveness and provide data about the sustainability of the effective benefit.”

The preclinical work that led to the clinical trial was also conducted in the Center for Gene Therapy in conjunction with Louise Rodino-Klapac, PhD, formerly a principal investigator. She now serves as the chief scientific officer at Sarepta Therapeutics, a leading developer for first-ever treatments for DMD and LGMD types 2D, 2B, 2E, 2L and 2C.